We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region.
Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10−8, and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19–1.40) and P= 7.63 × 10−10. An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.
Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology.
Cassava is a major source of food in tropical and subtropical regions. Here the authors sequence the genomes of wild and domesticated cassava varieties and identify genes that have been selected for and against during the evolution and domestication of this economically important crop.
The primary objective of this study investigated the role of microRNA-320 (miR-320) on left ventricular remodeling in the rat model of myocardial ischemia-reperfusion (I/R) injury, and we intended to explore the myocardial mechanism of miR-320-mediated myocardium protection. We collected 120 male Wistar rats (240–280 g) in this study and then randomly divided them into three groups: (1) sham surgery group (sham group: n = 40); (2) ischemia-reperfusion model group (I/R group: n = 40); and (3) I/R model with antagomir-320 group (I/R + antagomir-320 group: n = 40). Value changes of heart function in transesophageal echocardiography were recorded at various time points (day 1, day 3, day 7, day 15 and day 30) after surgery in each group. Myocardial sections were stained with hematoxylin and eosin (H&E) and examined with optical microscope. The degree of myocardial fibrosis was assessed by Sirius Red staining. Terminal dUTP nick end-labeling (TUNEL) and qRT-PCR methods were used to measure the apoptosis rate and to determine the miR-320 expression levels in myocardial tissues. Transesophageal echocardiography showed that the values of left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP) and ±dp/dtmax in the I/R group were obviously lower than those in the sham group, while the left ventricular end-diastolic pressure (LVEDP) value was higher than that in the sham group. The values of LVEF, LVFS, LVSP and ±dp/dtmax showed a gradual decrease in the I/R group, while the LVEDP value showed an up tendency along with the extension of reperfusion time. The H&E staining revealed that rat myocardial tissue in the I/R group presented extensive myocardial damage; for the I/R + antagomir-320 group, however, the degree of damage in myocardial cells was obviously better than that of the I/R group. The Sirius Red staining results showed that the degree of myocardial fibrosis in the I/R group was more severe along with the extension of the time of reperfusion. For the I/R + antagomir-320 group, the degree of myocardial fibrosis was less severe than that in the I/R group. Tissues samples in both the sham and I/R + antagomir-320 groups showed a lower apoptosis rate compared to I/R group. The qRT-PCR results indicated that miR-320 expression in the I/R group was significantly higher than that in both the sham and I/R + antagomir-320 groups. The expression level of miR-320 is significantly up-regulated in the rat model of myocardial I/R injury, and it may be implicated in the prevention of myocardial I/R injury-triggered left ventricular remodeling.
microRNA-320; myocardial ischemia-reperfusion injury; left ventricular remodeling
We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000–40,000. Only 2%–3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
Comparative genome sequencing of indica and japonica rice reveals that duplication of genes and genomic regions has played a major part in the evolution of grass genomes
Intravascular coronary stenting has been used in the treatment of coronary
artery disease (CAD), with a major limitation of in-stent restenosis (ISR).
The 316 stainless steel has been widely used for coronary stents. In this
study, we developed a novel coating method to reduce ISR by simultaneously
coating vascular endothelial growth factor (VEGF) and anti-CD34 antibody on
316L stainless steel.
Round 316L stainless steel sheets in the D-H group were polymerized with
compounds generated from condensation reaction of dopamine and heparin using
N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and
N-hydroxysuccinimide (NHS). Sixteen sheets from the D-H group were further
immersed into 1ug/ml VEGF165 and 3mg/ml heparin sodium one after
another for 10 times, and named as the D-(H-V)10 group. Eight
sheets from the D-(H-V)10 group were coated with anti-CD34
antibody and termed as the D-(H-V)10-A group. Immunofluorescence
assay and ELISA were used to evaluate whether the 316L stainless steel disks
were successfully coated with VEGF and anti-CD34 antibody.
The results of immunofluorescence assay and ELISA showed that VEGF could be
detected in the D-(H-V)10 and D-(H-V)10-A group,
suggesting the steel sheets were successfully covered with VEGF. Anti-CD34
antibody could only be observed in the D-(H-V)10-A group, which
was the only group coated with CD34 antibody. Both results suggested that
the 316L stainless steel sheets were successfully coated with VEGF and
Our study developed a method to simultaneously coat VEGF and anti-CD34
antibody to stainless metal steel. This research serves as a fundamental
role for a novel coating strategy.
Descriptors: Coronary Artery Disease. Drug-Eluting Stents.
Coronary Restenosis. Vascular Endothelial Growth Factor. Antigens, CD34.
Coronary Artery Disease; Drug-Eluting Stents; Coronary Restenosis; Vascular Endothelial Growth Factor; Antigens, CD34
Long-term noninvasive cell tracing by fluorescent probes is of great importance to life science and biomedical engineering. For example, understanding genesis, development, invasion and metastasis of cancerous cells and monitoring tissue regeneration after stem cell transplantation require continual tracing of the biological processes by cytocompatible fluorescent probes over a long period of time. In this work, we successfully developed organic far-red/near-infrared dots with aggregation-induced emission (AIE dots) and demonstrated their utilities as long-term cell trackers. The high emission efficiency, large absorptivity, excellent biocompatibility, and strong photobleaching resistance of the AIE dots functionalized by cell penetrating peptides derived from transactivator of transcription proteins ensured outstanding long-term noninvasive in vitro and in vivo cell tracing. The organic AIE dots outperform their counterparts of inorganic quantum dots, opening a new avenue in the development of fluorescent probes for following biological processes such as carcinogenesis.
Male breast carcinoma (MBC) is rarely encountered in clinical practice. Due to its paucity, our knowledge of MBC only rely on small or single-institutional studies and sporadic cases. The current guidelines for MBC are extrapolated from its female counterparts Rudlowski (Breast Care (Basel) 3(3):183–189, 2008). Nowadays, MBC is actively studied and viewed as a potentially different entity on the aspects of etiology, biological behavior and prognosis. Thus, special treatment strategy guidelines should be established for MBC. Additionally, advance in the systemic chemotherapy and hormonal therapy also contribute to the local control. The indication of radiotherapy need to be clarified and over-treatment should be avoided. Here we present two cases of MBC in which radiotherapy help to sustain a satisfactory disease free survival. Our cases will provide valuable experience for identifying the role of radiotherapy in MBC.
Male breast carcinoma; Radiotherapy
Purpose: A meta-analysis was undertaken to examine the correlation between ankylosing spondylitis (AS) progression and serum levels of pro-inflammatory cytokines, Interleukin-6 (IL-6) and Interleukin-17 (IL-17) in AS patients. Methods: PubMed, EBSCO, Cochrane Library database, Ovid, Springer link, WANFANG, China national knowledge infrastructure (CNKI) and VIP databases(last updated search in October, 2014) were exhaustively searched for published case-control studies using keywords related to IL-6, IL-17 and AS. The search results were screened using stringent inclusion and exclusion criteria, and the data from selected high-quality studies was analyzed with Comprehensive Meta-analysis 2.0 software. Results: Thirteen case-control studies were selected for this meta-analysis and contained a pooled total of 514 AS patients and 358 healthy controls. Our main result revealed strikingly higher serum levels of IL-6 and IL-17 in AS patients, compared to healthy controls (IL-6: SMD = 2.51, 95% CI = 1.33~3.70, P = 0.01; IL-17: SMD = 3.05, 95% CI = 2.09~4.02, P < 0.001). Ethnicity-based subgroup analysis showed a statistically correlation of high IL-6 and IL-17 serum levels with AS both in Asian (IL-6: SMD = 3.15, 95% CI = 0.75~5.55, P < 0.001; IL-17: SMD = 3.30, 95% CI = 1.93~4.66, P < 0.001) and Caucasian populations (IL-6: SMD = 1.34, 95% CI = 0.33~2.35, P = 0.009; IL-17: SMD = 2.52, 95% CI = 1.06~3.98, P = 0.001). Conclusion: Meta-analysis of pooled data from thirteen high-quality studies revealed a strong correlation between elevated IL-6 and IL-17 serum levels and the development of AS. Therefore, IL-6 and IL-17 could be used as markers for diagnosis and assessment of treatment outcomes in AS patients.
Ankylosing spondylitis; interleukin-6; interleukin-17; rheumatism; spondyloarthropathies; meta-analysis
The clinicopathological characteristics and rational treatment of primary laryngeal mucosa-associated lymphoid tissue (MALT) lymphoma are still unclear and need to be further defined due to the paucity of this separate lymphoma.
Herein, a supraglottic primary MALT lymphoma was described with detailed clinical course, intervention, and follow-up. To date, research of laryngeal MALT lymphoma has seldom been initiated. Our experience in this case will help to expand our understanding of this unique disease. A 58-year-old female presented with a history of progressive hoarseness for about 10 months. Multiple laryngoscopy examinations revealed severe hypertrophy of left ventricular band. She was admitted to our department with residual MALT lymphoma of supraglottic region after partial resection by laser. After systemic evaluation, she was staged as IEA, International Prognostic Index score 0. Irradiation of intensity modulated radiotherapy technique with a dose of 30.6 Gy/17f to the tumor and 25.5 Gy/17f to the related lymphatic drainage area achieved a complete remission. The disease-free survival has reached to 4 years. The irradiation related acute and late side effects were mild.
Radiotherapy is the first option for limited-stage primary laryngeal MALT lymphoma because of excellent treatment outcome.
Tissue engineering has brought new possibilities for the treatment of spinal cord injury. Two important components for tissue engineering of the spinal cord include a suitable cell source and scaffold. In our study, we investigated induced mouse embryonic fibroblasts (MEFs) directly reprogrammed into neural stem cells (iNSCs), as a cell source. Three-dimensional (3D) electrospun poly (lactide-co-glycolide)/polyethylene glycol (PLGA-PEG) nanofiber scaffolds were used for iNSCs adhesion and growth. Cell growth, survival and proliferation on the scaffolds were investigated. Scanning electron microcopy (SEM) and nuclei staining were used to assess cell growth on the scaffolds. Scaffolds with iNSCs were then transplanted into transected rat spinal cords. Two or 8 weeks following transplantation, immunofluorescence was performed to determine iNSC survival and differentiation within the scaffolds. Functional recovery was assessed using the Basso, Beattie, Bresnahan (BBB) Scale. Results indicated that iNSCs showed similar morphological features with wild-type neural stem cells (wt-NSCs), and expressed a variety of neural stem cell marker genes. Furthermore, iNSCs were shown to survive, with the ability to self-renew and undergo neural differentiation into neurons and glial cells within the 3D scaffolds in vivo. The iNSC-seeded scaffolds restored the continuity of the spinal cord and reduced cavity formation. Additionally, iNSC-seeded scaffolds contributed to functional recovery of the spinal cord. Therefore, PLGA-PEG scaffolds seeded with iNSCs may serve as promising supporting transplants for repairing spinal cord injury (SCI).
AIM: To investigate the clinical characteristics and prognostic factors of cutaneous metastasis of cholangiocarcinoma by a retrospective analysis of published cases.
METHODS: An extensive search was conducted in the English literature within the PubMed database using the following keywords: cutaneous metastasis or skin metastasis and cholangiocarcinoma or bile duct. The data of 30 patients from 21 articles from 1978 to 2014 were analyzed. Patient data retrieved from the articles included the following: age, gender, time cutaneous metastasis occurred, number of cutaneous metastases throughout life, sites of initial cutaneous metastasis, anatomic site, pathology and differentiation of cholangiocarcinoma, and immunohistochemical results of the cutaneous metastasis. The assessment of overall survival after cutaneous metastasis (OSCM) was the primary endpoint.
RESULTS: The median age at diagnosis of cutaneous metastasis of cholangiocarcinoma was 60.0 years (range: 35-77). This metastasis showed a predilection towards males, with a male to female ratio of 3.29. In 8 cases (27.6%), skin metastasis was the first sign of cholangiocarcinoma. Additionally, 18 cases (60.0%) manifested single cutaneous metastasis, while 12 cases (40.0%) demonstrated multiple skin metastases. In 50.0% of patients, the metastasis occurred in the drainage region, while 50.0% of patients had distant cutaneous metastases. The scalp was the most frequently involved region of distant skin metastasis, occurring in 36.7% of patients. The median OSCM of cholangiocarcinoma was 4.0 mo. Patient age and cutaneous metastatic sites showed no significant relation with OSCM, while male gender and single metastasis of the skin were associated with a poorer OSCM (hazard ratio: 0.168; P = 0.005, and hazard ratio: 0.296; P = 0.011, respectively).
CONCLUSION: The prognosis of cutaneous metastasis of cholangiocarcinoma is dismal. Both male gender and single skin metastasis are associated with a poorer OSCM.
Cutaneous metastasis; Cholangiocarcinoma; Clinical characteristics; Pathological features; Prognosis
Plasmablastic lymphoma (PBL) is an aggressive neoplasm exclusively occurring in AIDS patients. Recently, increasing cases of human immunodeficiency virus (HIV)-negative PBL have been reported. No standard therapy protocol is currently available since there is a great difference between PBL with and without HIV infection. Here, we present a rather rare case of HIV-negative PBL in the neck that dramatically responded to radiotherapy alone. Our case highlights the possibility of PBL in the neck and helps to expand our understanding of this separate lymphoma. The related literature review summarized the clinicopathological features and treatment status of HIV-negative PBL.
HIV-negative; Plasmablastic lymphoma; Radiotherapy
Solitary Fibrous Tumor of the Pleura (SFTP) is an uncommon neoplasm which grows slowly. For some cases, surgery is warranted. However, for unresectable ones, the standard strategy has not been established yet. We presented a rare case of recurrent malignant intrathoracic solitary fibrous tumor. It was impossible to resect the tumor. Radiotherapy alone achieved a significant improvement effect.
Radiotherapy; recurrent; solitary fibrous tumor of the pleura
AIM: To investigate the effects of dihydromyricetin (DHM) on the migration and invasion of human hepatic cancer cells.
METHODS: The hepatoma cell lines SK-Hep-1 and MHCC97L were used in this study. The cells were cultured in RPIM-1640 medium supplemented with 10% fetal bovine serum at 37 °C in a humidified 5% CO2 incubator. DHM was dissolved in dimethyl sulfoxide and diluted to various concentrations in medium before applying to cells. MTT assays were performed to measure the viability of the cells after DHM treatment. Wound healing and Boyden transwell assays were used to assess cancer cell motility. The invasive capacity of cancer cells was measured using Matrigel-coated transwell chambers. Matrix metalloproteinase (MMP)-2/9 activity was examined by fluorescence analysis. Western blot was carried out to analyze the expression of MMP-2, MMP-9, p-38, JNK, ERK1/2 and PKC-δ proteins. All data were analyzed by Student’s t tests in GraphPad prism 5.0 software and are presented as mean ± SD.
RESULTS: DHM was found to strongly inhibit the migration of the hepatoma cell lines SK-Hep-1 (without DHM, 24 h: 120 ± 8 μmol/L vs 100 μmol/L DHM, 24 h: 65 ± 10 μmol/L, P < 0.001) and MHCC97L (without DHM, 24 h: 126 ± 7 μmol/L vs 100 μmol/L DHM, 24 h: 74 ± 6 μmol/L, P < 0.001). The invasive capacity of the cells was reduced by DHM treatment (SK-Hep-1 cells without DHM, 24 h: 67 ± 4 μmol/L vs 100 μmol/L DHM, 24 h: 9 ± 3 μmol/L, P < 0.001; MHCC97L cells without DHM, 24 h: 117 ± 8 μmol/L vs 100 μmol/L DHM, 24 h: 45 ± 2 μmol/L, P < 0.001). MMP2/9 activity was also inhibited by DHM exposure (SK-Hep-1 cells without DHM, 24 h: 600 ± 26 μmol/L vs 100 μmol/L DHM, 24 h: 100 ± 6 μmol/L, P < 0.001; MHCC97L cells without DHM, 24 h: 504 ± 32 μmol/L vs 100 μmol/L DHM 24 h: 156 ± 10 μmol/L, P < 0.001). Western blot analysis showed that DHM decreased the expression level of MMP-9 but had little effect on MMP-2. Further investigation indicated that DHM markedly reduced the phosphorylation levels of p38, ERK1/2 and JNK in a concentration-dependent manner but had no impact on the total protein levels. In addition, PKC-δ protein, a key protein in the regulation of MMP family protein expression, was up-regulated with DHM treatment.
CONCLUSION: These findings demonstrate that DHM inhibits the migration and invasion of hepatoma cells and may serve as a potential candidate agent for the prevention of HCC metastasis.
Dihydromyricetin; Migration; Invasion; Hepatic cancer; Matrix metalloproteinase-9
Identification of protein binding sites is critical for studying the function of the proteins. In this paper, we proposed a method for protein binding site prediction, which combined the order profile propensities and hidden Markov support vector machine (HM-SVM). This method employed the sequential labeling technique to the field of protein binding site prediction. The input features of HM-SVM include the profile-based propensities, the Position-Specific Score Matrix (PSSM), and Accessible Surface Area (ASA). When tested on different data sets, the proposed method showed promising results, and outperformed some closely relative methods by more than 10% in terms of AUC.
We find that CsGAMYB1, a positive regulator of GA signalling, can regulate sex expression of cucumber. This provides a new insight into the mechanism of GA in sex determination.
Cucumber (Cucumis sativus L.) is a typical monoecious vegetable with individual male and female flowers, and has been used as a model plant for sex determination. It is well known that sex differentiation of cucumber can be regulated by phytohormones, such as gibberellic acid (GA) and ethylene. The molecular mechanism of female sex expression modulated by ethylene has been widely understood, but how GA controls male sex expression remains elusive. In hermaphroditic Arabidopsis and rice, GA can regulate stamen and anther development via the transcriptional regulation of GAMYB. Here we characterized a GAMYB homologue CsGAMYB1 in cucumber. We found that CsGAMYB1 is predominantly expressed in male flower buds, where its expression is upregulated by GA3 treatment. CsGAMYB1 protein is localized in the nucleus. CsGAMYB1 can partially rescue stamen development and fertility phenotypes of an Arabidopsis myb33 myb65 double mutant. However, constitutive overexpression of CsGAMYB1 in wild-type Arabidopsis resulted in male sterility, which mimics the effect of GA overdose in flower development. Knockdown of CsGAMYB1 in cucumber decreases the ratio of nodes with male and female flowers, and ethylene is not involved in this process. Our data suggest that CsGAMYB1 regulates sex expression of cucumber via an ethylene-independent pathway.
CsGAMYB1; cucumber; ethylene; GAMYB; gibberellin; sex expression.
Transcription activator-like effector nucleases (TALENs) are a powerful new approach for targeted gene disruption in various animal models, but little is known about their activities in Mus musculus, the widely used mammalian model organism. Here, we report that direct injection of in vitro transcribed messenger RNA of TALEN pairs into mouse zygotes induced somatic mutations, which were stably passed to the next generation through germ-line transmission. With one TALEN pair constructed for each of 10 target genes, mutant F0 mice for each gene were obtained with the mutation rate ranged from 13 to 67% and an average of ∼40% of total healthy newborns with no significant differences between C57BL/6 and FVB/N genetic background. One TALEN pair with single mismatch to their intended target sequence in each side failed to yield any mutation. Furthermore, highly efficient germ-line transmission was obtained, as all the F0 founders tested transmitted the mutations to F1 mice. In addition, we also observed that one bi-allele mutant founder of Lepr gene, encoding Leptin receptor, had similar diabetic phenotype as db/db mouse. Together, our results suggest that TALENs are an effective genetic tool for rapid gene disruption with high efficiency and heritability in mouse with distinct genetic background.
Cryptochromes are blue light receptors that mediate light regulation of gene expression in all major evolution lineages, but the molecular mechanism underlying cryptochrome signal transduction remains not fully understood [1, 2]. It has been reported that cryptochromes suppress activity of the multifunctional E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) to regulate gene expression in response to blue light [3, 4]. But how plant cryptochromes mediate light suppression of COP1 activity remains unclear. We report here that Arabidopsis CRY2 (cryptochrome 2) undergoes blue light-dependent interaction with the COP1-interacting protein SUPPRESSOR OF PHYTOCHROME A 1 (SPA1) [5, 6]. We demonstrate that SPA1 acts genetically downstream from CRY2 to mediate blue light suppression of the COP1-dependent proteolysis of the flowering-time regulator CONSTANS (CO) [7, 8]. We further show that blue light-dependent CRY2-SPA1 interaction stimulates CRY2-COP1 interaction. These results reveal for the first time a wavelength-specific mechanism by which a cryptochrome photoreceptor mediates light regulation of protein degradation to modulate developmental timing in Arabidopsis.
Genetic factors are thought to play a role in development for colorectal carcinogenesis. ICAM-1 is a polymorphic gene, thus, the present study investigated the relationship between the polymorphisms of ICAM-1 and the susceptibility and phenotypical characteristics of colorectal cancer (CRC).
The polymorphisms at ICAM-1 exon 4 (G241R) and exon 6 (E469K) were detected by PCR with sequence-specific primers. The relationship between specific genotypes of ICAM-1 and differentiation of CRC was evaluated by the histological grade.
We showed only GG genotype of ICAM-1 individuals in either CRC or normal controls. The KK genotype of ICAM-1 K469E was found more frequently than in the controls (P < 0.05). Patients with well-differentiated CRC displayed the KK more frequently than those of poor differentiation (P < 0.05).
The findings indicate that polymorphisms of G241R are rare in Chinese population and that KK genotype of ICAM-1 K469E is significantly associated with well differentiation of CRC.
Escherichia coli strains causing postweaning diarrhea (PWD) and edema disease (ED) in pigs are limited to a number of serogroups, with O8, O45, O138, O139, O141, O147, O149, and O157 being the most commonly reported worldwide. In this study, a DNA microarray based on the O-antigen-specific genes of all 8 E. coli serogroups, as well as 11 genes encoding adhesion factors and exotoxins associated with PWD and ED, was developed for the identification of related serogroups and virulence gene patterns. The microarray method was tested against 186 E. coli and Shigella O-serogroup reference strains, 13 E. coli reference strains for virulence markers, 43 E. coli clinical isolates, and 12 strains of other bacterial species and shown to be highly specific with reproducible results. The detection sensitivity was 0.1 ng of genomic DNA or 103 CFU per 0.3 g of porcine feces in mock samples. Seventeen porcine feces samples from local hoggeries were examined using the microarray, and the result for one sample was verified by the conventional serotyping methods. This microarray can be readily used to screen for the presence of PWD- and ED-associated E. coli in porcine feces samples.
The mechanism of action of artemisinin and its derivatives, the most potent of the anti-malarial drugs, is not completely understood. Here we present an unbiased chemical proteomics analysis to directly explore this mechanism in Plasmodium falciparum. We use an alkyne-tagged artemisinin analogue coupled with biotin to identify 124 artemisinin covalent binding protein targets, many of which are involved in the essential biological processes of the parasite. Such a broad targeting spectrum disrupts the biochemical landscape of the parasite and causes its death. Furthermore, using alkyne-tagged artemisinin coupled with a fluorescent dye to monitor protein binding, we show that haem, rather than free ferrous iron, is predominantly responsible for artemisinin activation. The haem derives primarily from the parasite's haem biosynthesis pathway at the early ring stage and from haemoglobin digestion at the latter stages. Our results support a unifying model to explain the action and specificity of artemisinin in parasite killing.
The mechanism of action of artemisinin, an antimalarial drug, is not well understood. Here, the authors use a labelled artemisinin analogue to show that the drug is mainly activated by haem and then binds covalently to over 120 proteins in the malaria parasite, affecting many of its cellular processes.
Mitochondria, vital organelles existing
in almost all eukaryotic cells, play a crucial role in energy metabolism
and apoptosis of aerobic organisms. In this work, we report two new
flavone-based fluorescent probes, MC-Mito1 and MC-Mito2, for monitoring mitochondria in living cells. These
two probes exhibit remarkably low toxicity, good cell permeability,
and high specificity; these probes complement the existing library
of mitochondrial imaging agents. The new dyes give nearly no background
fluorescence, and their application does not require tedious postwashing
after cell staining. The appreciable tolerance of MC-Mito2 encourages a broader range of biological applications for understanding
the cell degeneration and apoptosis mechanism.
imaging agents; fluorescence; mitochondria; flavone; biocompatibility; wash-free
The central mechanisms by which interleukin-1 beta (IL-1β) and angiotension II receptor 1 (AT1-R) contribute to sympathoexcitation in heart failure (HF) are unclear. In this study, we determined whether an interaction between IL-1β and AT1-R in the paraventricular nucleus (PVN) contributes to progression of HF. Rats were implanted with bilateral PVN cannulae and subjected to coronary artery ligation or sham surgery (Sham). Subsequently, animals were treated for 4 weeks through PVN infusion with either vehicle, losartan (LOS, 200 μg/day), IL-1β (IL, 1 μg/day), or IL-1β along with LOS (LOS+IL). HF rats had higher levels of corticotropin-releasing hormone (CRH), norepinephrine (NE), and glutamate (Glu); lower levels of gamma-aminobutyric acid (GABA); and more positive fra-like activity in PVN when compared with Sham rats. HF rats also had higher levels of NE, epinephrine (EPI), and IL-1β in plasma. PVN infusion of LOS attenuated the decreases in GABA and the increases in CRH, NE, and Glu in the PVN of HF rats. IL-1β could further increase the expression of CRH, NE, Glu, EPI, and IL-1β and decrease GABA expression. Treatment with IL-1β along with LOS could eliminate the effects of IL-1β. These findings suggest that an interaction between AT1-R and IL-1β in the PVN contributes to progression in HF.
A hydroxybenzohydrazide-based Schiff base ligand was conveniently synthesized. Upon addition of Zn2+ cation, the ligand exhibited a high tendency to form a binuclear structure with a 2:2 ligand-to-zinc ratio, which was accompanied with a large fluorescence turn-on (λem = 507 nm, ϕfl ≈ 0.28). The reactivity of zinc complex was examined by using different phosphate anions, which reveals a higher response to acid pyrophosphate anion. Detailed spectroscopic studies revealed that the pyrophosphate response is based on the ligand displacement mechanism.